Differentiation antagonizing non-protein coding RNA modulates the proliferation, migration, and angiogenesis of glioma cells by targeting the miR-216a/LGR5 axis and the PI3K/AKT signaling pathway

Wei Wang,1 Yulian Li,2 Qinghai Ma,3 Haicheng Yan,3 Wuyun Su11Department of Medical Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, People’s Republic of ChinaPurpose: DANCR plays an important role in various types of cancer. However, its role in gliomas remains unclear. In the present study, we aimed to investigate the mechanism underlying the role of DANCR in gliomas.Methods: DANCR expression was measured by qRT-PCR, and expression of LGR5, PI3K, AKT, and phosphorylated AKT (p-AKT) was detected by western blotting. The combination of miR-216a and DANCR was quantified by Luciferase reporter assays. Proliferation, apoptosis and cell cycle, migration and invasion, and angiogenesis of glioma cells were measured by MTT, flow cytometry, Transwell, and Tube formation assays, respectively.Results: DANCR expression was significantly higher in glioma cells than in normal human astrocytes. Silencing of DANCR inhibited proliferation, migration, invasion, and angiogenesis of glioma cells, promoted apoptosis, blocked the cell cycle at the G1/S transition, and reduced LGR5, PI3K, and p-AKT expression. We identified miR-216a as a direct target of DANCR. Silencing of DANCR in glioma cells increased miR-216a expression. Further, miR-216a suppression increased proliferation, migration, invasion, and angiogenesis and inhibited apoptosis of glioma cells transfected with DANCR-targeting siRNA. In addition, miR-216a suppression compromised inhibition of the G1/S transition caused by DANCR silencing. Furthermore, suppression of miR-216a increased accumulation of LGR5, PI3K, AKT, and p-AKT in glioma cells transfected with DANCR-targeting siRNA.Conclusion: DANCR modulates growth and metastasis by targeting the miR-216a/LGR5 axis and PI3K/AKT signaling pathway.Keywords: glioma, migration, invasion, angiogenesis, DANCR, miR-216